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Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women (ProBoneVSL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03165747
Recruitment Status : Terminated (Investigator terminated trial pursuant to research contract rights.)
First Posted : May 24, 2017
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
Roberto Pacifici, Emory University

Tracking Information
First Submitted Date  ICMJE May 23, 2017
First Posted Date  ICMJE May 24, 2017
Last Update Posted Date March 28, 2019
Actual Study Start Date  ICMJE October 1, 2017
Actual Primary Completion Date March 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2017)
Change in bone mineral density (BMD) of the lumbar spine (L1-L4 segment) as measured by DEXA (dual energy X-ray absorptiometry). [ Time Frame: Baseline and 12-month visit. ]
All DEXA scans will be performed on the same device using a GE Lunar iDEXA machine. Participants will be asked to lie still on a scanning table with their arms at their sides for approximately 10 minutes.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03165747 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2017)
  • Change in bone density of the non-dominant hip (femoral neck and total hip area) as measured by DEXA (dual energy X-ray absorptiometry). [ Time Frame: Baseline and 12-month visit. ]
    All DEXA scans will be performed on the same device using a GE Lunar iDEXA machine. Participants will be asked to lie still on a scanning table with their arms at their sides for approximately 10 minutes.
  • Change in serum collagen type 1 cross-linked C-telopeptide (CTX) concentrations (a marker of bone resorption). [ Time Frame: Baseline, 6-month, 12-month visits ]
    Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
  • Change in serum procollagen type I N propeptide (PINP) - a marker of bone formation - concentrations. [ Time Frame: Baseline, 6-month, 12-month visits ]
    Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
  • Change in serum free receptor activator of nuclear factor kappa-B ligand (RANKL) concentrations. [ Time Frame: Baseline, 6-month, 12-month visits ]
    Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
  • Change in serum osteoprotegrin (OPG) concentrations. [ Time Frame: Baseline, 6-month, 12-month visits ]
    Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
  • Change in serum tumor necrosis factor-TNF. [ Time Frame: Baseline, 6-month, 12-month visits ]
    Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
  • Change in serum interleukin-17 (IL-17) concentrations. [ Time Frame: Baseline, 6-month, 12-month visits ]
    Up to approximately 50 mL of fasted blood will be collected at every visit from a peripheral vein.
  • Number of unused study drug satchets. [ Time Frame: Every two weeks during the study 12-months ]
    This will be determined by contacts (twice monthly telephone or at research center visits) of the study coordinator with each subject and responses to three standardized question areas: 1) "Are you having any difficulty, problems or new symptoms with the study medication?" 2) If yes, "What has the problem been?" and 3) "Have you missed any of your study drug doses, and if so how many in the previous 2 week period?" Appropriate notations based on subject responses will be documented in the case report form (CRF). Subjects will be instructed at study entry and reminded via serial contacts to return all of their used and unused drug sachets at each research center visit. Unused and used study drug satchets will be tallied and recorded in the CRF by the study coordinator serially for the entire study.
  • Gastrointestinal Symptom Rating [ Time Frame: Every two weeks during the study 12-months ]
    Study drug tolerance will be assessed by obtaining serial measures of the Gastrointestinal Symptom Rating Scale (GSRS). These will be obtained with in-person interviews at the baseline and month 6 and 12 visits and by telephone contact with all subjects by the study coordinator every 2 weeks. Data will be analyzed within the 5 symptom domains depicting symptoms related to gastric reflux, abdominal pain, indigestion, diarrhea, and constipation.The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. A GSRS total score, the sum of all 5 domains, will also be assessed.
  • Study retention rate. [ Time Frame: Up to 12 months ]
    The number of participants who complete all study visits, phone calls, and maintain drug compliance. Retention will be documented via conventional Consolidated Standards of Reporting Trials (CONSORT) criteria and documentation of missed study visits, missed telephone communications and compliance with study drug administration. All data will be maintained in the CRFs.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women
Official Title  ICMJE Effect of VSL#3 on Bone Mineral Density in Postmenopausal Women: a Pilot Randomized, Placebo-Controlled Trial
Brief Summary

Osteoporosis has a devastating impact on quality of life of postmenopausal women, and is a significant cause of disability and morbidity. Many drugs are approved for the prevention and treatment of osteoporosis, but are associated with high costs and side effects. Some data from animal studies suggests that supplementation with probiotics can safely treat and prevent osteoporosis. The probiotic VSL#3 is commercially available, is safe for human consumption, and has been widely used in human clinical trials, and has known health-promoting effects in both children and adults.

The double-blind, randomized, placebo-controlled trial of VSL#3 will be conducted for 12 months in 40 postmenopausal women to determine if VSL#3 improves bone mineral density and related bone markers. Study visits will include all or some of the following procedures: a medical exam, urine collection, height and weight measurement, a blood draw to assess bone biomarkers, a DEXA (dual energy X-ray absorptiometry) scan to measure bone density, and health questionnaires.

This is one of the first clinical trials proposed to investigate the effects of probiotics in bone in humans. If successful, this proposal will provide the first evidence that nutritional supplementation with the probiotic VSL#3 is a safe and effective strategy for preventing postmenopausal bone loss.

Detailed Description

Osteoporosis has a devastating impact on quality of life of postmenopausal women, and is a significant cause of disability and morbidity. Many drugs are approved for the prevention and treatment of osteoporosis, but are associated with high costs and side effects. Some data from animal studies suggests that supplementation with probiotics can safely treat and prevent osteoporosis. The probiotic VSL#3 is commercially available, is safe for human consumption, and has been widely used in human clinical trials, and has known health-promoting effects in both children and adults.

The double-blind, randomized, placebo-controlled trial of VSL#3 will be conducted in a population of ambulatory, otherwise healthy, postmenopausal women for 12 months. Control and VSL#3-treated postmenopausal women will be matched by age (± 3 years). Study visits will include all or some of the following procedures: a medical exam, urine collection, height and weight measurement, a blood draw to assess bone biomarkers, a DEXA (dual energy X-ray absorptiometry) scan to measure bone density, and health questionnaires.

The primary endpoint is the change in bone mineral density (BMD) at the L1-4 lumbar spine over one year of study. Changes in BMD at the femoral neck and total hip area will be secondary endpoints. All BMD data will also be used as a tool for future studies power calculation and design. Additional endpoints will include changes in bone turnover markers and inflammatory/osteoclastogenic cytokines. Measurements of indices of bone turnover and cytokine levels will provide much needed mechanistic information.The data will allow to establish whether VSL#3 prevents bone loss and/or increases bone mass by regulating bone resorption, formation, or both.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Only the IDS pharmacy will know which dose of probiotic was given to the subject. The study team, parents, subjects, individuals entering the data, statistician, individuals performing laboratory tests and DEXA (dual energy X-ray absorptiometry) scans, research center nurses and investigators will remain blinded as to which treatment the subjects received. Each subject will be assigned a unique identifier, which will be used in the database. In addition, all lab specimens will only include the patient's unique identifier. Permuted block sizes will not be disclosed to the blinded study personnel to minimize the likelihood of their being able to predict the next randomization assignment in the series. Investigators and all study personnel will remain blinded until the final subject has completed her final visit and primary and secondary endpoints have been analyzed.
Primary Purpose: Prevention
Condition  ICMJE Menopausal Osteoporosis
Intervention  ICMJE
  • Drug: VSL#3
    8 strains of live bacteria: Bifidobacterium breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. bulgaricus and Streptococcus thermophilus. 900 billion CFU taken orally daily in a single administration.
  • Other: Placebo
    Two placebo sachets taken orally daily in a single administration.
Study Arms  ICMJE
  • Experimental: VSL#3
    VSL#3 two active sachets [containing 450x109 colony-forming units (CFU)/sachet], taken daily in a single administration.
    Intervention: Drug: VSL#3
  • Placebo Comparator: Control
    Placebo, no supplemental probiotics.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 12, 2019)
35
Original Estimated Enrollment  ICMJE
 (submitted: May 23, 2017)
40
Actual Study Completion Date  ICMJE March 23, 2019
Actual Primary Completion Date March 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Willing and able to give written informed consent for participation in the study,
  2. Age range 50-65 years,
  3. Menopausal status (defined by >1 yr since last menstrual period or FSH level in the postmenopausal range),
  4. Ambulatory,
  5. Body mass Index (BMI) must be ≥ 18 and ≤ 32 kg/m2 at screening,
  6. Bone mineral density (BMD), expressed as T-scores, must be > - 2.5 in the lumbar spine (L1-L4), the femoral neck, and the total hip, as measured by dual energy X-ray absorptiometry (DXA),
  7. Commitment not to use any products that may influence the study outcome (see below),
  8. Ability to understand and comply with the requirements of the study.

Exclusion Criteria:

  1. Premenopausal status,
  2. History of >1 previous atraumatic bone fractures after age 50;
  3. Presence of established osteoporosis (T-score ≤ - 2.5, in the lumbar spine, femoral neck or total hip as measured by screening DXA),
  4. History of immunological or bone-related disorders including: HIV infection, Type I diabetes mellitus, bone marrow or organ transplantation; Inflammatory bowel disease (ulcerative colitis, Crohn's disease); multiple myeloma; osteomalacia; osteosarcoma; Paget's disease; rheumatoid arthritis; systemic lupus erythematous; parathyroid disorders,
  5. Uncontrolled type II diabetes mellitus (HgbA1c ≥ 7% within the last 12 months),
  6. History of bariatric surgery or other forms of malabsorption (including documented celiac disease, or chronic diarrhea),
  7. Alcohol abuse,
  8. Clinically significant chronic kidney disease (stage ≥ 2, with total serum creatinine level > 2.5 mg/dL and calculated glomerular filtration rate (GFR) < 60 mL/min by the Modification of Diet in Renal Disease (MDRD equation),
  9. Clinically significant cardiovascular disease (myocardial infarction, cerebral vascular accident or acute congestive heart failure within the previous 12 months,
  10. Any malignancies, other than localized skin squamous cell carcinoma, diagnosed within the previous 5 years, or any history of metastatic cancer,
  11. History of use of oral supplement products containing probiotic bacteria (more than once per week) within four weeks prior to baseline,
  12. Current use (within the past 8 weeks) of any medication with known influences on the immune or skeletal system (e.g. immune modulation therapy, systemic glucocorticoids, systemic steroid hormones,
  13. Use of oral or injectable bisphosphonates for more than 1 year within the last 5 years,
  14. Current or past use (within 1 year) of Denosumab, Teriparatide, Raloxifene, hormone replacement therapy (HRT), calcitonin, or any other anti-resorptive agent other than bisphosphonates used for the prevention and treatment of osteoporosis,
  15. Use of antibiotics during the previous two months or frequent user of antibiotics (>2 courses during the previous 12 months) for any cause,
  16. Smoking or use of nicotine-containing products during the last six months,
  17. Known hypersensitivity to any of the ingredients in the VSL#3 or the placebo study drug,
  18. serum or plasma 25-hydroxyvitamin D [25(OH)D] concentration < 12 ng/mL,
  19. uncontrolled thyroid disease (abnormal blood TSH level within the last 12 months and/or changing dose of thyroid replacement therapy within the last 12 months).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Females
Ages  ICMJE 50 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03165747
Other Study ID Numbers  ICMJE IRB00095798
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Roberto Pacifici, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Roberto Pacifici Emory University
PRS Account Emory University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP